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1.
J Hepatol ; 79(1): 167-180, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36996943

RESUMO

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) is characterised by a defect in arterial oxygenation induced by pulmonary vascular dilatation in patients with liver disease. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, suppresses vasodilation by reducing nitric oxide (NO) production. We investigated the role of S1P in patients with HPS and the role of fingolimod as a therapeutic option in an experimental model of HPS. METHODS: Patients with cirrhosis with HPS (n = 44) and without HPS (n = 89) and 25 healthy controls were studied. Plasma levels of S1P, NO, and markers of systemic inflammation were studied. In a murine model of common bile duct ligation (CBDL), variations in pulmonary vasculature, arterial oxygenation, liver fibrosis, and inflammation were estimated before and after administration of S1P and fingolimod. RESULTS: Log of plasma S1P levels was significantly lower in patients with HPS than in those without HPS (3.1 ± 1.4 vs. 4.6 ± 0.2; p <0.001) and more so in severe intrapulmonary shunting than in mild and moderate intrapulmonary shunting (p <0.001). Plasma tumour necrosis factor-α (76.5 [30.3-91.6] vs. 52.9 [25.2-82.8]; p = 0.02) and NO (152.9 ± 41.2 vs. 79.2 ± 29.2; p = 0.001) levels were higher in patients with HPS than in those without HPS. An increase in Th17 (p <0.001) and T regulatory cells (p <0.001) was observed; the latter inversely correlated with plasma S1P levels. In the CBDL HPS model, fingolimod restored pulmonary vascular injury by increasing the arterial blood gas exchange and reducing systemic and pulmonary inflammation, resulting in improved survival (p = 0.02). Compared with vehicle treatment, fingolimod reduced portal pressure (p <0.05) and hepatic fibrosis and improved hepatocyte proliferation. It also induced apoptotic death in hepatic stellate cells and reduced collagen formation. CONCLUSIONS: Plasma S1P levels are low in patients with HPS and even more so in severe cases. Fingolimod, by improving pulmonary vascular tone and oxygenation, improves survival in a murine CBDL HPS model. IMPACT AND IMPLICATIONS: A low level of plasma sphingosine-1-phosphate (S1P) is associated with severe pulmonary vascular shunting, and hence, it can serve as a marker of disease severity in patients with hepatopulmonary syndrome (HPS). Fingolimod, a functional agonist of S1P, reduces hepatic inflammation, improves vascular tone, and thus retards the progression of fibrosis in a preclinical animal model of HPS. Fingolimod is being proposed as a potential novel therapy for management of patients with HPS.


Assuntos
Síndrome Hepatopulmonar , Ratos , Camundongos , Animais , Síndrome Hepatopulmonar/tratamento farmacológico , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/uso terapêutico , Ratos Sprague-Dawley , Cirrose Hepática/complicações , Niacinamida/uso terapêutico , Inflamação/complicações
2.
J Clin Exp Hepatol ; 14(6): 101473, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070155

RESUMO

Background/Aims: To study the association of infertility in patients with Budd Chiari syndrome, radiological aspects of the disease determining infertility and to see if there are improved chances of conception following radiological intervention. Methods: Retrospective search of the hospital records was done and patients with Budd Chiari syndrome, who underwent radiological intervention between January 2016 till October 2021 were initially included. Patients outside the reproductive age group, unmarried patients, patients who did not attempt conception or attempted for less than 1 year and patients having other causes of infertility were excluded. 90 patients were assessed for presence of primary or secondary infertility using infertility questionnaire. In patients with infertility, conception during 1-year follow-up period following radiological intervention, was assessed. Results: 146 patients underwent radiological intervention for Budd Chiari syndrome in the study period. 56 patients meeting the exclusion criteria were excluded from the study and subsequently 90 patients were assessed for infertility. 16.7% (15/90) of our patients with Budd Chiari syndrome had infertility, of which 7 were male, and 8 were female. Infertility is more common in younger age group (mean - 28.8 ± 4.2 years) (P < 0.001). In females, presence of pelvic venous congestion on preprocedural imaging showed significant association with infertility (P < 0.001). 6 (40%) out of 15 of patients with infertility conceived during a 1-year follow-up period after radiological intervention. Conclusion: Infertility is a common in patients with Budd Chiari syndrome, with a prevalence of 16.7%. Pelvic venous congestion is associated with women having infertility. Radiological interventions play important role in management of Budd Chiari and may help to overcome infertility in these patients.

3.
Diagnostics (Basel) ; 13(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36766542

RESUMO

PURPOSE: To study the prevalence of back pain in patients of Budd-Chiari syndrome (BCS) with inferior vena cava (IVC) obstruction, and to evaluate the role of IVC recanalization in resolution of back pain. METHODS: All patients with BCS and IVC obstruction who underwent IVC recanalization between January 2018 and October 2022 were included. Patients with degenerative spine disease or other identifiable causes for back pain were excluded; remaining patients were assessed for the presence of back pain. In patients with back pain, pain relief was assessed at 24 h following IVC recanalization. RESULTS: Fifty-eight patients with BCS and IVC occlusion were identified, of which six with degenerative spine diseases were excluded. Of the remaining 52 patients, 34 (65.4%) had back pain, with pain score between 3 and 9. Engorged epidural venous plexus on preprocedural imaging (p = 0.002), and degree of luminal narrowing (p = 0.021) had a significant association with back pain. Twenty-nine of thirty-four patients (85.3%) with back pain had pain relief immediately following IVC recanalization, more so in patients with engorged epidural venous plexus on preprocedural imaging (p < 0.001). CONCLUSION: Back pain is one of the under-reported symptoms of IVC obstruction in BCS. IVC recanalization by IVC angioplasty with or without stenting relieves back pain due to the decompression of engorged epidural veins.

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